title: Progress in dodecafluoropentane emulsion as a neuroprotective agent in a rabbit stroke model.
abstract: Dodecafluoropentane emulsion (DDFPe) in 250 nm nanodroplets seems to swell modestly to accept and carry large amounts of oxygen in the body at >29 °C. Small particle size allows oxygen delivery even into hypoxic tissue unreachable by erythrocytes. Using permanent cerebral embolic occlusion in rabbits, we assessed DDFPe dose response as a neuroprotectant at 7 and 24 h post-embolization without lysis of arterial obstructions and investigated blood pharmacokinetics. New Zealand White rabbits (N = 56) received cerebral angiography and embolic spheres (diameter = 700-900 μm) occluded middle and/or anterior cerebral arteries. Intravenous DDFPe dosing (2 % w/v emulsion) began at 60 min and repeated every 90 min until sacrifice at 7 or 24 h post-embolization. Seven-hour groups: (1) control (embolized without treatment, N = 6), and DDFPe treatment: (2) 0.1 ml/kg (N = 7), (3) 0.3 ml/kg (N = 9), (4) 0.6 ml/kg (N = 8). Twenty-four-hour groups: (5) control (N = 16), and DDFPe treatment: (6) 0.1 ml/kg (N = 10). Infarcts as percent of total brain volume were determined using vital stains on brain sections. Other alert normal rabbits (N = 8) received IV doses followed by rapid arterial blood sampling and GC-MS analysis. Percent infarct volume means significantly decreased for all DDFPe-treated groups compared with controls, p = <0.004 to <0.03. Blood DDFP (gas) half-life was 1.45 ± 0.17 min with R = 0.958. Mean blood clearance was 78.5 ± 24.9 ml/min/kg (mean ± SE). Intravenous DDFPe decreases ischemic stroke infarct volumes. Blood half-life values are very short. The much longer therapeutic effect, >90 min, suggests multiple compartments. Lowest effective dose and maximum effective therapy duration are not yet defined. Rapid development is warranted.
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, USA, CulpWilliamC@uams.edu.
authors.forename: S D
authors.initials: SD
authors.lastname: Woods
authors.forename: R D
authors.initials: RD
authors.lastname: Skinner
authors.forename: A M
authors.initials: AM
authors.lastname: Ricca
authors.forename: A T
authors.initials: AT
authors.lastname: Brown
authors.forename: J D
authors.initials: JD
authors.lastname: Lowery
authors.forename: M J
authors.initials: MJ
authors.lastname: Borrelli
authors.forename: J O
authors.initials: JO
authors.lastname: Lay
authors.forename: W C
authors.initials: WC
authors.lastname: Culp
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004655:Emulsions; D005466:Fluorocarbons / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D010420:Pentanes
chemical_list: D004655:Emulsions; D005466:Fluorocarbons; D018696:Neuroprotective Agents; C008806:perfluoropentane; D010420:Pentanes